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Mining Stored-Specimen Studies for Information about Cancer Natural History.

The advent of new multicancer early detection tests and publication of early diagnostic results have generated expectations of clinical benefit from multicancer screening. The clinical benefit of a cancer screening test depends critically on disease natural history, which is typically learned from prospective screening studies. Retrospective studies of stored blood specimens are important in learning about a test's preclinical diagnostic performance but have rarely been used to infer natural history. The extent to which these studies might be harnessed to also learn natural history is discussed in the context of an article in this issue that infers the combined natural history of a range of cancers targeted by a multicancer early detection test using a case-control subsample of specimens from a large cohort study. The critical question concerns the identifiability of key transition rates in multistate models of natural history alongside state-specific sensitivities. The article suggests that these parameters are estimable within a Bayesian framework that leverages prior information about test sensitivity from diagnostic studies. We offer a heuristic discussion of identifiability in this setting and encourage formal study to determine the extent to which models with varying degrees of complexity may be learned from stored-specimen studies. See related article by Dai et al., p. 1535.

Humans

An impact assessment of the European medical device regulations implementation - the current status quo.

BACKGROUND: This research aims to assess the current impact of the medical and in-vitro diagnostic devices regulations (MDR/IVDR) on the device industry in the EU, under the lens of postimplementation and the amending regulation, and in advance of the final transition to the IVDR/MDR in the future. RESEARCH DESIGN AND METHODS: A quantitative survey was administered to a diverse cohort of medical device enterprises, ranging from micro to large organizations. RESULTS: The survey indicates that the MDR/IVDR has harmed innovation, leading many manufacturers to seek initial device approval and launch elsewhere before in Europe. There is evidence that some manufacturers have rationalized their existing product portfolios and removed devices from the market as they stated they would in previous industry surveys. The MDR/IVDR has been shown to negatively impact manufacturers, with increased costs related to notified body (NB) fees, maintaining and updating documentation, recertification fees, and hiring additional staff. CONCLUSION: This study provides a current status of the effects of MDR/IVDR on manufacturers and finds that despite amending regulations and other interventions taken by the EU to mitigate regulatory burden, ensure product availability, and address stakeholder concerns, the EU is no longer the market of choice for new products.

Equipment and Supplies

Plant cis-regulatory grammar: Decoding the multidimensional code of transcriptional regulation for programmable crop engineering.

Cis-regulatory elements (CREs) orchestrate the spatiotemporal precision of gene expression that underlies plant development, adaptation, and domestication. Decoding the cis-regulatory grammar of plant genomes remains a central challenge in modern biology, with profound implications for programmable crop engineering. Here, recent conceptual and technological advances are synthesized to reshape our understanding of plant CREs. This review first argues that CRE function is not only an intrinsic property of DNA sequence alone but also emerges from a multidimensional context, including chromatin accessibility, histone modifications, three-dimensional genome topology, and cell type-specific regulatory landscapes. Furthermore, the convergence of single-cell epigenomics, high-throughput functional assays, and CRISPR-based dissection has begun to unravel this contextual grammar, revealing the computational principles governing transcriptional regulation. Critically, we propose that artificial intelligence (AI) platforms are catalyzing an ongoing transition from descriptive discovery to predictive engineering, wherein these platforms outperform natural evolution in designing synthetic CREs. Finally, a roadmap is outlined toward a plant regulatory grammar foundation model, which will enable truly predictive engineering of gene expression when fine-tuned for specific tasks. Collectively, the integration of single-cell resolution maps, precise genome editing, AI-driven design, and regulatory-compliant delivery systems promises to transform our ability to reprogram plant gene regulation for next-generation agriculture, bridging the gap between foundational regulatory biology and tangible crop improvement.

artificial intelligence

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is molecularly and immunologically heterogeneous, contributing to variable treatment response. Because regulated cell death (RCD) intersects with tumor metabolism, immune regulation, and therapeutic susceptibility, we built an RCD-centered framework for CRC stratification. Multi-cohort transcriptomic data were used to infer RCD subtypes with non-negative matrix factorization (NMF) and non-negative least squares (NNLS). Genomic, bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets were integrated to characterize subtype-associated biology. Machine-learning models were developed for immunotherapy response and survival-risk estimation. Candidate compounds were screened by GDSC2-based drug-sensitivity modeling and molecular docking, and FSTL3 was functionally assessed in vitro. The framework separated CRC samples into two RCD-related phenotypes resembling immune-hot and immune-cold states. RCD1 showed immune activation and higher mutational burden, whereas RCD2 showed immune-suppressed features, intratumoral heterogeneity, and aggressive biology. RCD-associated signatures showed potential for predicting immunotherapy response and survival risk. Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses.

Colorectal cancer

Recent advances in Strongyloides screening, diagnostics, therapeutics, and management.

PURPOSE OF REVIEW: Strongyloidiasis affects an estimated 30-100 million people globally and can have life-threatening consequences in immunocompromised hosts, yet it remains underdiagnosed due to limited access and performance of available diagnostics. Novel assays and anthelmintics may reshape screening, diagnosis, treatment, and prevention for at-risk populations. RECENT FINDINGS: Advances in molecular diagnostics coupled with robust stool extraction methods have supplanted traditional parasitologic methods in settings where nucleic acid amplification is feasible. Transition from standard immunoglobulin G (IgG)-based immunoassays to the new IgG- and IgG4-based rapid diagnostic tests using recombinant Strongyloides stercoralis nematode immunodominant E antigen (NIE) and/or S. stercoralis immunoreactive antigen (SsIR) has facilitated serologic screening at the point of care. The World Health Organization now conditionally recommends community-wide ivermectin mass drug administration in highly endemic settings. Regarding new treatment options, moxidectin is noninferior to ivermectin with 93-94% cure rates and a longer half-life, while emodepside shows 80-90% predicted cure rates in early trials and offers a mechanistically distinct option. Understanding of immunosuppressed populations at risk for hyperinfection has expanded, prompting updated screening recommendations. SUMMARY: Serologic and molecular tools are improving screening and diagnosis, and moxidectin and emodepside may broaden treatment options, but data in severe disease and special populations remain limited. Priorities include harmonized screening algorithms and prospective studies in high-risk groups.

Humans

TWIST2-dependent transcriptional activation of TPI1 mediates TGF-β1-driven fibroblast activation in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by aberrant profibrotic signaling and excessive extracellular matrix deposition, accompanied by fibroblast-to-myofibroblast transition. Despite extensive investigation, the molecular mechanisms underlying IPF pathogenesis remain incompletely understood. Here, we investigated the role of triosephosphate isomerase 1 (TPI1) in IPF progression and its regulation by transforming growth factor-β (TGF-β) signaling. Loss-of-function analyses identified TPI1 as a downstream effector of TGF-β1, as its knockdown markedly suppressed fibrotic marker expression, fibroblast proliferation, and migration. Mechanistically, TWIST2 was shown to function as a direct transcriptional regulator of TPI1, binding to its promoter and promoting transcriptional activation. Rescue experiments further confirmed that the TWIST2-TPI1 axis is central to the progression of pulmonary fibrosis. Notably, knockdown of either TPI1 or TWIST2 effectively attenuated TGF-β1-induced fibrotic phenotypes. Collectively, these findings define the TGF-β1/TWIST2/TPI1 signaling axis as an important regulator of pathogenic fibroblast behavior and pro-fibrotic responses through transcriptional control of TPI1, highlighting its potential as a therapeutic target for IPF.

Twist-Related Protein 1

Retention strategies and participant retention rates among prospective longitudinal pregnancy cohorts: a systematic mapping review.

Prospective longitudinal pregnancy cohorts can answer questions about fetal and early life exposures and later health outcomes; however, there are challenges to retaining participants in longitudinal studies, particularly over life transitions like the birth of a child. Optimal methods for retaining participants in longitudinal research are unclear. A systematic mapping review was conducted to identify prospective cohort studies and randomized controlled trials that enrolled pregnant participants and their infants. Data on retention rates and 17 retention strategies was extracted. A random effects meta-analysis generated pooled annual retention rates inversely weighted to the number of baseline participants. Spearman rank coefficients were used to assess correlation between strategy use and retention. A random-effects meta-regression was used to determine if select retention strategies were associated with participant retention. We identified 130 studies, involving 472 022 pregnancies. A downward trend in pooled mean retention rates were observed. Studies utilized an average of 6.8 (SD 3.9) retention strategies. Statistically significant associations were not observed between strategy use and retention rates at follow-up (p > 0.05). Prospective studies of pregnant people and their infants used multiple retention strategies. Participant retention rates declined over time, suggesting that additional factors may influence study participation in the postpartum period.

Humans

A translational framework for early-phase inner-ear gene therapy: clinical trial design, regulatory strategy, and ethical considerations.

PURPOSE OF REVIEW: Hereditary hearing loss has historically been approached as a diagnostic category rather than a therapeutically modifiable disease. Recent advances in molecular genetics, cochlear gene delivery, and first-in-human clinical trials are changing that. This review summarizes contemporary progress in the genetics of hearing loss, with emphasis on emerging gene-based therapies, clinical trial design, regulatory and ethical considerations, and practical implications for otolaryngologists as biologic treatment enters clinical practice. RECENT FINDINGS: Early clinical trials targeting OTOF -related DFNB9 deafness have demonstrated satisfactory safety profiles and meaningful auditory recovery, establishing the first proof-of-concept for cochlear gene therapy in humans, culminating in the April 2026 FDA approval of Otarmeni. Genetic diagnoses are increasingly informing prognosis, cochlear implant counseling, and therapeutic candidacy. Preclinical research continues to expand toward recessive, dominant, and syndromic hearing loss using gene replacement, antisense, RNA interference, and genome-editing strategies. Substantial challenges remain, including heterogeneous outcome measures, uncertain long-term efficacy, regulatory complexity, and inequitable global access. SUMMARY: The genetics of hearing loss is transitioning from a diagnostic modality to an interventional one. Widespread clinical impact will require advances in vector engineering, equitable implementation, multidisciplinary counseling, and integration with established rehabilitation pathways. For otolaryngologists, genetic literacy is becoming essential to contemporary hearing care.

Humans

Risk factors for bleeding after endoscopic retrograde cholangiopancreatography: a systematic review and meta-analysis.

BACKGROUND AND AIMS: ERCP is associated with adverse events, including bleeding, which occurs in up to 1.3% of cases. This meta-analysis aims to identify and quantify risk factors associated with post-ERCP bleeding. METHODS: A comprehensive literature search of electronic databases was conducted from inception to January 10, 2025. Studies were eligible if they used multivariate analysis to identify predictors of post-ERCP bleeding. Risk factors reported in at least 2 studies were pooled using a random-effects model to calculate odds ratios (ORs) with 95% CIs. A further subgroup analysis was performed, including risk factors for postsphincterotomy bleeding and postendoscopic papillectomy bleeding. RESULTS: Twenty-seven studies (4 prospective and 23 retrospective studies) comprising 149,870 patients were included, of whom 1865 experienced post-ERCP bleeding. Twenty potential risk factors were analyzed. The meta-analysis identified several factors significantly associated with increased odds of post-ERCP bleeding in the pooled adjusted analysis, including male gender (OR, 1.24; 95% CI, 1.05-1.46), anticoagulation therapy (OR, 2.75; 95% CI, 1.66-4.56), cirrhosis (OR, 2.54; 95% CI, 1.76-3.65), hemodialysis (OR, 5.82; 95% CI, 3.32-10.18), coagulopathy (OR, 11.01; 95% CI, 2.50-48.40), endoscopic sphincterotomy (EST) (OR, 3.19; 95% CI, 1.69-6.01), precut sphincterotomy (OR, 2.24; 95% CI, 1.52-3.30), and intraoperative bleeding (OR, 2.57; 95% CI, 1.80-3.66). Several factors in the pooled adjusted analysis were not found to be significantly associated with higher odds of post-ERCP bleeding, including high body mass index (BMI), nonsteroidal anti-inflammatory drug (NSAID) use, antiplatelet therapy, thrombocytopenia, common bile duct stones, cholangitis, endoscopic papillary balloon dilatation, and covered self-expandable metal stent insertion. CONCLUSIONS: This meta-analysis identified that the anticoagulation therapy, cirrhosis, hemodialysis, coagulation disorder, EST, precut sphincterotomy, and male gender are associated with increased odds of post-ERCP bleeding in the pooled adjusted analysis. Conversely, age, high BMI, cholangitis, choledocholithiasis, pancreatic duct stones, needle-knife sphincterotomy, NSAID use, and antiplatelet therapy were not significantly associated with higher odds of post-ERCP bleeding in the pooled adjusted analysis. Incorporating our results into a prediction model may assist in identifying patients at increased risk, optimizing informed consent, and guiding prevention and management strategies for post-ERCP bleeding.

Humans

Innovations in microbial physical mutagenesis for food fermentation: An overview from traditional to emerging technologies.

Microbial strains serve as an important factor affecting fermentation efficiency and product quality. To obtain superior strains, mutation breeding is a classic strategy. Compared to chemical mutagenesis, physical mutagenesis directly induces genomic changes, providing notable advantages such as the elimination of chemical residues and environmental sustainability, hence rendering it a favored method for enhancing food-grade microorganisms. Conventional physical mutagenesis mostly depends on UV, rays, high pressure, or space radiation. As physical technologies advance, emerging methods such as ion implantation, plasma, microwave, ultrasound, and pulsed light are widely utilized for genetic modification. Mutagenesis technologies are progressively transitioning from single-effect to multi-effect synergy. Recent evaluations indicate that emerging technologies can enhance microbial mutation efficiency at the application level relative to established technologies. Nonetheless, the systematic clarification and comparative analysis at the mechanistic level remain inadequate, hindering intuitive comprehension of the qualities and distinctions across techniques. Furthermore, physical mutagenesis encounters several significant obstacles, such as cellular damage, limited rates of advantageous mutations, and laborious screening processes. This review carefully elucidates the mechanisms and properties of physical mutagenesis technology and delineates the distinctions among approaches through comparative analysis. Simultaneously, solutions for optimizing mutagenesis are presented to tackle the principal challenges mentioned above. This review aims to offer a theoretical foundation and practical guidance for the enhanced application of physical mutagenesis technologies in microbial breeding.

Mutagenesis

Complicated urinary tract infections: evolving definitions, clinical burden, and treatment landscape amid antimicrobial resistance.

INTRODUCTION: Complicated urinary tract infection (cUTI) is a common and heterogeneous infection associated with substantial morbidity, high healthcare utilization, and increasing antimicrobial resistance. Evolving definitions, increasing device use, and changing patient populations have altered its epidemiology and management. Marked variability in diagnostic criteria, clinical trial endpoints within and outside registrational settings, and treatment strategies complicates clinical decision-making and interpretation of therapeutic advances. AREAS COVERED: This review examines contemporary cUTI epidemiology, classification frameworks, and drivers of disease burden. It evaluates resistance trends and their therapeutic implications, alongside stewardship-based management strategies, including empiric antibiotic selection, intravenous-to-oral transition, treatment duration, and source control. Challenges in catheter-associated infection, recurrence, and regulatory endpoint design are discussed, together with the emerging role of novel agents targeting resistant Gram-negative pathogens. EXPERT OPINION: Rising multidrug resistance and limited oral options are reshaping cUTI management, necessitating individualized, stewardship-aligned therapy guided by illness severity and local epidemiology. Current regulatory endpoints inadequately reflect patient-centered outcomes, particularly in the context of asymptomatic bacteriuria. Expanding availability of effective oral agents may enable earlier discharge and outpatient care. Integration of rapid diagnostics and risk stratification will be essential to optimize therapy, limit resistance, and improve outcomes.

Humans

Identification of the BrSK gene family in flowering Chinese cabbage and functional characterization of BrSK2 subfamily involvement in heat stress.

Glycogen synthase kinase 3 (GSK3) kinases are evolutionarily conserved regulators of plant development and stress signaling, yet their contributions to thermotolerance in cool-adapted Brassica crops remain poorly understood. Here, we identified 16 BrSK genes in the Caixin (Brassica rapa ssp. chinensis var. parachinensis) genome, all harboring intact catalytic motifs indicative of functional kinase activity. Spatiotemporal expression profiling revealed preferential accumulation of BrSK transcripts in stem apices and floral organs during reproductive transition, while promoter analysis identified abundant heat- and abiotic stress-responsive cis-elements. Under heat stress, BrSK21, BrSK22, and BrSK23 displayed striking genotype-specific expression dynamics. BrSK21/22/23 transcripts were stably suppressed in the heat-tolerant cultivar '49-19' but transiently declined before rapidly rebounding in the heat-sensitive 'Liuye 50', mirroring RNA-seq profiles. Protein-protein interaction assays (Y2H, BiFC, and LCI) demonstrated specific associations between BrSK kinases and BrHSFA1. Functional validation via VIGS revealed that silencing of BrSK21 significantly enhanced thermotolerance, with triple silencing of BrSK21/22/23 conferring additive protection, indicating functional redundancy within the BrSK2 subfamily. Collectively, these findings establish the BrSK2 subfamily as negative regulators of heat tolerance in Caixin, likely via modulation of BrHSFA1 expression. This work identifies high-priority targets for molecular breeding of climate-resilient Brassica vegetables.

Plant Proteins

Morphological changes and transcriptomic insights into skeletal development of embryos and larvae of the sea urchin Strongylocentrotus intermedius.

To explore morphological features and molecular dynamics underlying skeletogenesis in the sea urchin Strongylocentrotus intermedius, we conducted combined morphological observation and comparative transcriptome analyses across representative embryonic and larval developmental stages. Morphological results showed that triradiate spicules first emerged at the gastrula stage. The 8-arm pluteus stage was identified as a key phase for skeletal remodeling, during which new three-radiate crystals transformed into complex stereoscopic ossicles including tube feet, spines and test plates. Transcriptomic data indicated that most differentially expressed genes (DEGs) were downregulated from the blastula to gastrula. The altered expression of basal metabolic genes and extracellular matrix genes including Colp2α and calm may be correlated with the linear mineralization of early spicules, which potentially reflects an energy adjustment pattern in developing larvae. During the transition from 6-arm to 8-arm pluteus, expression changes of calmodulin-like, Colp2α and SISin18G001660 suggest potential associations with regional calcium deposition and modifications of skeletal matrix properties. This work systematically characterizes morphological traits and transcriptional dynamics of skeletogenesis in S. intermedius. Its early spiculogenesis follows the conserved developmental pattern of echinoderms, while massive formation of stereoscopic ossicles occurs at the 8-arm pluteus stage. Stage-specific transcriptional changes across key larval skeletogenic stages are uncovered, offering transcriptomic resources for functional verification of skeletal regulatory genes.

Animals

Integrative analysis of transcriptome and DNA methylome dynamics during caudal fin regeneration in silver pomfret (Pampus argenteus).

Caudal fin regeneration in teleost fish is a complex, multi-stage process involving coordinated molecular and cellular changes. While the role of epigenetic regulation particularly DNA methylation has been studied in model freshwater species such as zebrafish, its contribution to regeneration in marine teleosts remains largely unexplored. In this study, we integrated transcriptomic and DNA methylomic data to characterize the temporal dynamics of gene expression and methylation during caudal fin regeneration in the silver pomfret (Pampus argenteus). Using RNA-sequencing and reduced representation bisulfite sequencing (RRBS) at three biologically critical time points 1, 3, and 7 days post-amputation (dpa), we characterized the spatiotemporal molecular landscape of caudal fin regeneration. These time points capture the key transitional phases of wound healing and inflammation (1 dpa), blastema formation and progenitor proliferation (3 dpa), and regenerative outgrowth with tissue remodeling (7 dpa), enabling robust detection of the major molecular programs underlying epimorphic regeneration. Concurrently, CG-methylome analysis identified thousands of dynamically changing differentially methylated regions (DMRs). A strong global inverse correlation was observed between promoter methylation and gene expression. Integrative analysis pinpointed key regeneration genes (fgf20a, msxb, sox9b) whose expression was associated with dynamic methylation changes in their promoters or gene bodies. We conclude that DNA methylation is a dynamic and key regulatory layer that acts in concert with transcriptional reprogramming to coordinate tissue regeneration, providing new insights into the epigenetic mechanisms underlying complex regenerative processes in teleosts.

Animals

Mechanisms linking the gut microbiota to colorectal cancer development and progression.

Colorectal cancer remains a leading cause of global cancer mortality, with a concerning rise in early-onset cases driven by complex interactions between environmental exposures, lifestyle factors, and host genetics. Mounting evidence indicates that gut microbiota dysbiosis critically modulates this oncogenic process, acting as an active participant rather than a passive bystander. This review systematically synthesizes the dichotomous roles of the intestinal microbiome in colorectal tumorigenesis through the conceptual framework of the driver-passenger model. We discuss how early initiating driver bacteria, such as Polyketide synthase-positive Escherichia coli and enterotoxigenic Bacteroides fragilis, compromise mucosal barriers, induce chronic mucosal inflammation, and inflict direct genomic instability. As the local tumor microenvironment undergoes profound metabolic remodeling, opportunistic passenger pathogens, notably Fusobacterium nucleatum, become enriched, further promoting cellular proliferation and facilitating tumor immune evasion. Conversely, protective commensals, exemplified by Clostridium butyricum and Streptococcus thermophilus, exert robust tumor-suppressive effects through multifaceted mechanisms. These beneficial microbes actively antagonize malignant progression by redirecting tumor metabolic fluxes toward oxidative stress, orchestrating deep epigenetic reprogramming, and degrading core oncoproteins to reverse chemoresistance. Transitioning from fundamental mechanisms to clinical application, we evaluate a comprehensive spectrum of microbiota-targeted interventions, encompassing non-invasive diagnostic biomarkers, fecal microbiota transplantation, engineered bacteria, phage therapy, and postbiotics. Finally, we critically address the formidable translational challenges associated with microbial heterogeneity, long-term safety, and regulatory standardization, aiming to provide a balanced perspective on integrating microbiome-based strategies into next-generation precision oncology for colorectal cancer.

Humans

Time Heals Some Wounds? Burnout but Not Secondary Traumatic Stress in Critical Care Nurses.

BACKGROUND: Burnout among new nurses has been widely documented. Less is known about how years of professional experience relate to distinct components of professional quality of life, including compassion satisfaction and secondary traumatic stress. Early-career nurses appear particularly vulnerable to occupational strain, warranting examination of how years of experience may influence perceptions of professional well-being. OBJECTIVE: To examine the relationship between years of nursing experience and professional quality of life among critical care nurses. METHODS: A quantitative, cross-sectional pilot study was conducted using the Professional Quality of Life scale. A convenience sample of 55 nurses were recruited and consented from a rural hospital in the western United States. Descriptive statistics and Pearson correlations were used to examine relationships between years of experience and scores on the instrument's subscales. RESULTS: Forty nurses provided complete survey responses. Years of nursing experience correlated positively with compassion satisfaction and negatively with burnout. No significant relationship was found between years of experience and secondary traumatic stress. CONCLUSIONS: Greater professional experience was associated with higher compassion satisfaction and lower burnout but not with secondary traumatic stress. These findings suggest that experience may buffer against cumulative occupational strain, whereas trauma-related stress responses may persist across career stages. Structured mentoring and transition support may help to mitigate burnout among early-career nurses, and trauma-informed leadership approaches may warrant consideration in high-acuity environments.

Humans

Microbial diversity, functional activities, and safety risks in fermented tea: a comprehensive review.

Microbial fermented teas are gaining global popularity due to their unique sensory profiles and health benefits. The quality and safety of these products are governed by complex microbial ecosystems that orchestrate the biotransformation of tea leaf components. This review addresses a critical paradox in the field: the same microbial activities that generate desirable bioactive metabolites, such as theabrownins and organic acids, also create ecological niches for mycotoxigenic fungi, posing significant health risks from contaminants like ochratoxin A, citrinin, and aflatoxins. While extensive research has cataloged the microbial diversity in these systems, a comprehensive framework linking processing environments to microbial community assembly, functional outcomes, and quantifiable safety risks remains elusive. This review systematically bridges this gap by synthesizing current knowledge on the microbial consortia-dominated by Aspergillus, Penicillium, Bacillus, and Lactiplantibacillus species-that drive tea fermentation. We critically analyze their functional roles in enhancing flavor, bioactivity, and potential probiotic activity while simultaneously evaluating the mechanisms of mycotoxin production and accumulation. By integrating microbial ecology, biochemistry, and food safety, we propose a forward-looking perspective focused on transitioning the industry from traditional, spontaneous fermentation to modern, controlled biotechnological processes. This approach, centered on the use of defined starter cultures, predictive modeling, and active biocontrol strategies, provides a roadmap for ensuring the consistent quality and safety of fermented tea products, ultimately unlocking their full potential as high-quality functional foods.

Tea

Epitranscriptomic erasers in bivalves: Evolutionary divergence and species-specific transcriptional plasticity of the ALKBH family under acute thermal stress.

The AlkB homolog (ALKBH) family of Fe(II)/α-ketoglutarate-dependent dioxygenases mediates nucleic acid demethylation, thereby governing RNA metabolism and genomic stability. Despite their pivotal roles in epitranscriptomic regulation across vertebrates, the evolutionary dynamics and functional significance of ALKBH proteins in bivalve mollusks remain largely unexplored. Here, we present a comprehensive phylogenomic analysis of 210 ALKBH genes identified across 35 bivalve species. Our analyses reveal a distinct evolutionary trajectory characterized by the lineage-specific loss of ALKBH4 and the restricted distribution of ALKBH5 to the Mytilidae family, contrasting sharply with vertebrate repertoires. Using the noble scallop (Chlamys nobilis) and Pacific oyster (Crassostrea gigas) as model systems, we demonstrate that ALKBH genes exhibit conserved spatiotemporal expression patterns, with pronounced enrichment in gonadal tissues and during metamorphic transitions, implicating these enzymes in gametogenesis and larval development. Furthermore, comparative thermal stress experiments reveal divergent transcriptional plasticity: the subtropical scallop C. nobilis mounts rapid, transient induction of ALKBH1/2/6 under heat shock, whereas the eurythermal oyster C. gigas maintains sustained ALKBH3 expression, potentially underpinning its superior thermal tolerance. Conversely, cold stress elicits bimodal regulation in C. nobilis, with ALKBH1/2 upregulation contrasting with ALKBH6/7/8 suppression. These findings illuminate the functional diversification of bivalve ALKBH genes and their potential utility as molecular biomarkers for assessing developmental competence and thermal resilience in shellfish aquaculture.

Animals